Itching, or pruritus, is a pervasive and often distressing sensation that prompts the desire to scratch. While most cases of persistent itching are caused by common skin conditions, dry skin, or allergic reactions, an unexplained, generalized itch can sometimes indicate an underlying systemic illness. When this symptom occurs without a primary skin rash and is directly related to a malignancy, it is often categorized as a paraneoplastic syndrome, meaning the cancer itself, or the body’s reaction to it, is causing the irritation.
Cancers Most Commonly Associated with Itching
Itching is a notable symptom across various types of cancer, but it is disproportionately associated with cancers of the blood and lymph system. Hematological cancers, such as lymphomas and leukemias, are the most frequent cause of cancer-related pruritus. This type of systemic itch is typically widespread and can be present for months or even years before a cancer diagnosis is made.
Hodgkin Lymphoma is perhaps the classic example, where severe, generalized itching is a well-recognized “B-symptom” that can accompany fever and night sweats. In Hodgkin Lymphoma, the itch is often intense, predominantly affecting the lower limbs and sometimes leading to significant sleep disruption. Other lymphoproliferative diseases, including various forms of Non-Hodgkin Lymphoma and leukemia, also frequently present with this symptom.
Another distinct category is the myeloproliferative neoplasms, a group of slow-growing blood cancers, most notably Polycythemia Vera (PV). A characteristic symptom in PV is aquagenic pruritus, an intense itch that is specifically triggered by contact with water, regardless of the temperature.
Solid tumors generally cause pruritus less frequently, but when they do, the mechanism is usually localized and related to obstruction. Cancers of the liver, bile duct, gallbladder, and pancreas can cause a blockage in the flow of bile. This obstruction leads to a buildup of bile acids in the bloodstream, which then deposit in the skin and irritate cutaneous nerve endings. While less common, certain primary skin cancers, such as Basal Cell Carcinoma and Squamous Cell Carcinoma, can also be associated with localized itching at the tumor site.
The Biological Basis for Cancer-Related Itching
The underlying causes of cancer-related pruritus are complex and vary depending on the type of malignancy, often involving a systemic release of chemical mediators. In lymphomas and leukemias, the cancer cells or the immune cells reacting to them release substances that act directly on the nervous system. These pruritogenic mediators include cytokines, such as Interleukin-31, which is heavily implicated in the severe itching seen in cutaneous T-cell lymphomas.
Other chemical signals involved are histamine and serotonin, which directly stimulate unmyelinated C-nerve fibers in the skin, sending itch signals to the brain. Endogenous opioids, which are naturally produced by the body, can also contribute to the sensation of itch by interacting with opioid receptors on sensory nerves. The itch associated with cancer is often considered “non-histaminergic,” meaning it does not respond well to traditional antihistamine medications.
The mechanism for solid tumors causing cholestasis is distinct and involves the accumulation of bile salts. When a tumor obstructs the bile ducts, bile, which is produced by the liver to aid digestion, cannot drain properly. The resulting increase in serum bile acids leads to their deposition in the dermis, where they act as direct irritants to the sensory nerve endings. This systemic buildup can also cause jaundice, characterized by yellowing of the skin and eyes, which frequently accompanies the obstructive itch.
Itching can also arise as a secondary systemic effect of advanced disease. Conditions like severe anemia, or the impaired function of organs such as the kidneys or liver, can cause generalized dryness (xerosis) and subsequent itching. Kidney failure, a complication of some cancers or their treatments, is a known cause of chronic, generalized pruritus.
Treatment Strategies for Pruritus Caused by Cancer
Managing cancer-related pruritus requires a two-pronged approach: addressing the underlying malignancy and providing symptomatic relief for the persistent itch. The most definitive and effective treatment for paraneoplastic pruritus is often the successful treatment of the cancer itself. When the tumor burden is reduced through chemotherapy, radiation, or surgery, the systemic release of the itch-inducing mediators subsides, leading to a resolution of the symptom.
For immediate relief and management while the underlying disease is being treated, several symptomatic options are available. Simple measures include:
- Maintaining a cool environment.
- Wearing loose-fitting clothing.
- Rigorously applying emollients to counteract dry skin.
- Using topical corticosteroids to treat areas of inflammation.
- Applying lotions containing menthol or camphor for a temporary cooling and soothing effect.
Since much of the cancer-related itch is not mediated by histamine, traditional antihistamines often offer limited effectiveness. Medications that target the nervous system are frequently used for better results, such as the neuroleptic agents gabapentin or pregabalin, which work by modulating nerve signals. In cases where the itch is thought to involve the opioid system, a mu-opioid receptor antagonist like naltrexone may be prescribed.
For the specific pruritus caused by bile duct obstruction and cholestasis, bile acid sequestrants like cholestyramine are used to bind bile acids in the gut and promote their excretion. A newer class of medication, the NK-1 receptor antagonist aprepitant, has also shown promise for refractory cases of cancer-related pruritus by blocking a neuropeptide involved in the itch pathway.